Blocking c-kit activity prevents pulmonary hypertension and 5-HT2BR overexpression. Groups of 10 WT mice were exposed to hypoxia (10% 0₂) for 5 weeks (H), and in the presence of either RS-127445 (0.5 mg/kg-HRS), or STI-571 (1 mg/kg-HST) and compared with normoxic mice (0). (A) The significant increase in hypoxia-induced RVSP was totally prevented by RS-127445 or STI-571. (B) Chronic hypoxia increased significantly the maximal number of lung 5-HT_2BR specific binding sites (Bmax), which was not significantly prevented by RS-127445, but STI-571 did prevent this increase. (C) Groups of 10 WT mice were exposed to hypoxia (10% 0₂) for 0 to 35 days in the presence of vehicle (Veh) or STI-571 (STI; 1 mg/kg). The significant increase in hypoxia-induced RVSP observed at 21 and 35 days was totally prevented by STI-571 with similar kinetic. (D) Chronic hypoxia increased significantly the maximal number of lung 5-HT_2BR specific binding sites (Bmax) at 21 and 35 days, which was significantly prevented by STI-571 with similar kinetic. Values are means ± SEM (n = 10, P < .05), and are representative of at least 2 independent experiments. Straight lines are normoxic values. Any statistical difference by 1-way ANOVA followed by Bonferroni posthoc test versus normoxic untreated control values is indicated by * and versus chronic hypoxia values by a #; ***P < .001; **P < .01; *P < .05; ##P < .01; #P < .05.